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Tuesday 26 April 2016

Mediterranean diet score in stable heart disease, and, more thoughts on Ramsden et al.

This news article that made the rounds yesterday demonstrates how confirmation bias keeps the diet-heart hypothesis afloat.

Healthy eating key to heart disease

After 3.7 years' follow-up, a heart attack, stroke or death - termed a major adverse cardiac event - had occurred in 10.1 per cent of the participants. Such events occurred in 7.3 per cent of the people in the highest Mediterranean-diet bracket, 10.5 per cent in the next bracket down and 10.8 per cent in those who ate smaller quantities of the healthier foods.

"After adjusting for other factors that might affect the results we found that every one unit increase in the Mediterranean diet score was associated with a 7 per cent reduction in the risk of heart attacks, strokes or death from cardiovascular or other causes in patients with existing heart disease," Mr Stewart said.

The elements of the Mediterranean Diet Score can be found in the full paper and supplementary tables. It turns out foods like dairy, eggs, and tofu were also found to be protective but weren't included in the Med diet score; whereas lower meat intake wasn't protective but was included; and wholegrains weren't protective, but were included. Go figure.

Auckland University heart disease researcher, Professor Rod Jackson noted that the authors did not report on saturated fat consumption or fat consumption at all because they stated it had not been recorded reliably.

"However, the findings are quite consistent with the standard diet-heart hypothesis. A Mediterranean diet is low in saturated fat and was associated with lower risk of CHD [coronary heart disease].

"The Western diet score was based on consumption of refined carbohydrates, sweets and desserts, sugared drinks and deep-fried food. None of these foods except deep-fried foods, and only if the fat was saturated, are associated with CHD. They are associated with overweight/obesity and diabetes but the pro-fat lobby have always confused the issue by wrongly lumping obesity and diabetes with CHD.

" ... they are very different conditions and are trending in opposite directions."

This association of saturated fat and CHD seems to be a bit imaginary, but what is the explanation for junk foods having no association with CHD?
Well firstly, this was a very crude data collection effort, even by diet epidemiology standards. Many foods either weren't measured or were tucked away in the nearest category.
Secondly, because it depends on "diet scores" to aggregate non-significant associations, the non-significant association between deep fried food (the biggest source of omega-6 PUFA here) and CHD has been overlooked.
Thirdly, if you're going to eat less junk food, it is possible to replace it with "healthy" foods that aren't associated with benefit here. Namely wholegrain products, which are the densest calorie source in the Med diet score category. Imagine someone eating fewer biscuits and replacing that with wholemeal muffins. You could replace sugar-sweetened soft drink with fruit juice too - I'm not sure if that fits anywhere in these scores.Fourthly, this survey took place during another massive failed drug trial. A drug supposed to protect those with stable heart disease did diddly-squat. This data was salvaged from the wreckage. That's not a confounder that I can see, but I do find it interesting that this bit of context didn't make the papers.
Fifthly, there are some huge differences in smokers, BMI, education and income between the higher vs lower Med diet score groups. If these are associated with junk food intake and you're correcting for them, then you're correcting for a large association in the hope of leaving a smaller one intact. It's a wonder, with all its flaws, that this study arrived at any result resembling a plausible reality. But it did, in my opinion.


I wrote a letter to the Herald about this yesterday, but it wasn't published today, so here it is.

Dear sir,

     The standard diet-heart hypothesis says that saturated fat in the diet causes heart disease by raising LDL cholesterol. This notion has taken a bit of a drubbing recently, so it is understandable that Professor Rod Jackson interprets yesterday’s study, about a higher Mediterranean diet score protecting against heart attacks, strokes, and deaths in those with stable heart disease, in its favour. 
     However, this ignores two findings from this study; firstly, that the mean LDL cholesterol level was not significantly different (2.3 vs 2.2 mmol/L) across the “Mediterranean diet score” categories, and secondly, that the two traditional food sources of saturated fat measured, meat and dairy, were not associated with increased risk; in fact dairy was associated with reduced risk.
     Although wholegrains were included in the Mediterranean diet score, they were not associated with benefit by themselves, and it would, for instance, be possible from this data to show that a “Paleolithic diet score” of eggs, meat, fruit, vegetables and fish, but no grains, was associated with as much benefit as the Mediterranean diet score. Furthermore, the two Mediterranean foods which the earlier PrediMed intervention identified as being most beneficial, olive oil and nuts, were not even measured in the new study.
     The one reliable finding from this study is that, the more minimally processed, nutrient-dense foods you include in your diet, the healthier it is. Maybe this should be the new diet-heart hypothesis until a better one comes along.

yours, etc

Ramsden et al has been the gift that keeps on giving. I had some more thoughts about the kind of problems a high omega-6 intervention might run into which I appended to Steven Hamley's analysis of the MCE study here. The FADS2 polymorphism study I refer to is this one.

I notice that those defending omega 6 interventions in the BMJ rapid responses have cited the Farvid et al meta-analysis of observational studies. However Farvid et al did not control for omega 3 fatty acids at all and this is quite clearly stated, so cannot be cited to refute any Ramsden et al meta-analysis.
Further, this is a bizarre procedure. If experiments don't confirm observations from population studies, you can't just cite another population study to refute the experiments. Prof Brunner does this in the rapid responses using quite a minor observational study that used "dietary pattern" analysis, with a healthy "dietary pattern" including margarine, to refute the experiments. If this is the procedure of epidemiologists, no wonder we are where we are with this zombie hypothesis.

Edit: I dug up the Whitehall II study that Prof Brunner cited, and which he co-authored.

Increased CHD risk (hazard ratio for top quartile: 2.01, 95%CI 1.41-2.85, adjusted for age, sex, ethnicity and energy misreporting) was observed with a diet characterised by high consumption of white bread, fried potatoes, sugar in tea and coffee, burgers and sausages, soft drinks, and low consumption of French dressing and vegetables."
This was dietary pattern 1.
A higher score on dietary pattern 1 was associated with higher total cholesterol, lower HDL cholesterol and higher triglycerides. Dietary pattern 2 was characterised by higher consumption of red meat, cabbage, brussels sprouts and cauliflower, and lower consumption of wholemeal bread, jam, marmalade and honey, tofu and soy, buns, cakes, pastries, fruit pies and polyunsaturated margarine.
A higher score on dietary pattern 2 was associated with higher total cholesterol and higher triglycerides. 
Dietary pattern 2 showed a significant linear trend across quartiles with a higher dietary pattern score also associated with increased risk of CHD (Model 3, adjusted for age, sex and energy misreporting, ethnicity, employment grade, smoking, alcohol and physical activity, p less than 0.0001) however this relationship was no longer significant after further adjustment for BMI and blood pressure.(As far as I can see, the pattern 2 trend was never very significant and the dose-response of both patterns is all over the place. There are 6 possible statistical models for each pattern, and none in the table given reads as having anything like a 0.0001 p value).

The paper states that French dressing (21% PUFA according to wikipedia) had no independent association with CHD, and gives no information about independent associations with polyunsaturated margarine.

Sunday 10 April 2016

The Tragedy of William Stark, who conclusively proved that eating crap will kill you, by a process of self-experimentation, in 1770, a fact which more people should pay attention to.

How did I not know about William Stark MD?

Born in Birmingham of an Irish mother and a Scottish father, he studied philosophy in Glasgow and medicine in Edinburgh and at the University of Leiden before going to work as a doctor in London in 1765.

"The person on whom these experiments are tried is a healthy man, about twenty-nine years of age, six feet high, stoutly made, but not corpulent, of a florid complexion, with red hair."
However, the Doctor who attended his final hours writes "He was of a fair complexion, tall, of a thin make, and healthful."

In 1769 Stark began a series of dietary experiments with observations on the effects of bread and water over a two week period. He included data about the weather, weight loss or gain, stool number and characteristics, and sexual frequency (was there an unfortunate Mrs Stark?).

He followed this up - without a break or ""washout" period of normal diet - with bread, water and 4oz and 8 oz of sugar daily.

During the third period of this experiment he one day ate some meat, and drank some wine. At the end of this second fortnight Stark felt "perfectly hearty, my head clear, often hungry, but never had any desires."

Stark's subsequent experiments are too many to list, but included flour and suet, flour and olive oil (he gained the same amount of weight on each). By now he has scurvy - his gums are black and he has lost a tooth, which began to hurt on the sugar diet. Then he began to live freely on animal food, milk and wine, and recovered his health and spirits - but not for long. Thinking that his afflictions were in fact due to sugar, Stark resolved to test this hypothesis with a return to the bread, sugar, and water diet, eating 6 oz sugar per day over 5 days without his gums being affected, but with the usual loss of desire. For a week in November 1769 he ate bread, beef and water, and "on the third day of this period I began to have desires, which were considerable in the night. On the fifth day, Venus semel". (Semel means once in latin; the expression Venus bis, or twice, appears more often in the text).

Stark then tries living only on lean, well-boiled beef, with its gravy (cooking water and juices).
"In two or three hours after a meal of ten or twelve ounces of meat with its gravy, I became hungry, and was particularly so every night at bed-time. I never had any wind in my stomach, and very seldom passed any downwards. My spirits, at all times very good, were somewhat raised after each meal; but my sleep was every night disturbed by dreams, a circumstance which was new to me. I commonly awoke very early in the morning, and found myself lively and well refreshed : and although I had not slept my usual time, I was never drowsy of an evening. I had sometimes weak desires at the beginning of this period, but none afterwards. My stools resembled in colour, the rust of iron."

For the next 5 days he added fat to the beef, and slept more soundly. He then spent 2 weeks on flour and suet, in order to compare the effect of flour with that of lean beef.
"During the second period I found the diet begin to disagree with me -, I lost my appetite, and was seized with severe head-achs, with uneasiness at my stomach and bowels, and great part of the tallow passed through my body assimilated. I was thirsty, and greatly troubled with wind, upwards and downwards. I also at this time observed a considerable increase in my urine.

Having been extremely uneasy during the night of the second of December, and having no appetite for food on the morning of the  third, I thought proper, though my appetite returned in the afternoon, to abstain from food the whole day, and next morning was quite well.
      Suspecting that the bad effects of the preceding diet were owing to the quantity, and not the quality of the tallow, I diminished the quantity during the last period, and had then the satisfaction to find the diet agree with me perfectly well. My bowels were quite easy, and I was not troubled with wind, with thirst, or with head-aches, and no part of the tallow remained undigested."
Over Christmas of 1769, Stark enjoyed a diet of flour and marrow oil.
"I found myself remarkably well on this regimen, and thought my spirits raised by it ; though this might be only opinion, as it is difficult on such Subjects to distinguish between fancy and reality. I sometimes had desires. Venus semel, during the first period.
Finding the oil of marrow so mild in the bowels, and at the same time so agreeable a food, I increased it".

After trying suet again, he notes "Is it not evident, then, that an excess in the use of oils, is more hurtful to the body, than an excess in any other article of food ? and that, of course, we ought to be particularly careful in regulating the quantity and quality of the oils we employ in diet."

Remember those words. On February the 4th 1770 Stark began a diet of bread and honey, which caused him considerable internal distress, then followed it with bread and 4oz Cheshire cheese for 2 days. This left him "feeble, uneasy, sighing and moaning". He wrote,
"Does not an excess in sweets give a still greater shock to the constitution than an excess in fats? Is there any other article of food so hurtful as either, taken immoderately?"
He took his last meal, of bread and rosemary tea, on the 18th February 1770, while a hurricane raged outside.

The doctor who attended him wrote "For several months before his death he had been employed in making experiments upon himself, of the effects of different kinds of food ; among the last was that of honey and flour made into a pudding, upon which he had lived several days, and which seemed to be extremely diuretic at first, as he made considerably more water than the liquor he drank. At last it brought on a diarrhoea, for which he ate Cheshire cheese, to the quantity of a quarter of a pound, without any other food, and that seemed to bind his body so much that he had not been at stool for five days. When he was taken ill, on Sunday, the 18 th of February, 1770, he sent for Mr. Hewson to bleed him, when he complained of his head and in his belly. The blood was somewhat fizzy."

William Stark died on the 23rd February 1770. His friend James Carmichael Smith, who became Physician Extraordinary to the King, posthumously edited his papers into this 1788 edition. It includes many pages of statistical tables recording his observations. 

Stark even measured his perspiration in the last days of his life.
Stark's death is attributed to scurvy, as can be seen by the restorative effect on his health when his diet included meat or fruit, but that's probably not the whole story. He proved to my satisfaction that you need to watch what you eat if you want to stay alive; that animal foods are a blessing, and that, if you wish to continue in desire and keep your teeth, beware the grains and sugars, and be particularly careful in regulating the quantity and quality of added fats and oils.

Thursday 7 April 2016

On second thoughts, that vegetarian genomic study did show that not eating animals is not good for you.

Generally, a study that purported to show that vegan and vegetarian diets are harmful would be welcomed by meat eaters, who get a lot of pseudoscientific criticism from members of those groups, some of it disguised as sober science.
But no-one was much impressed by the Pune vs. Kansas study. Even Tom Naughton wrote it off as meaning the same thing the head of the NZ vegetarian society said it meant - that omega-6 seed oils just aren't good for us anyway.

But I thought about this, and, not so fast.
Seed oils high in omega 6 are harmful for the descendants of long lines of vegetarians because such people, because of an adaptation to the virtual absence, from their diets, of DHA and AA (arachidonic acid), the very long-chain PUFAs found in animal flesh and organ meats, have a more efficient version of the genes involved in synthesizing these fats from alpha-linolenic acid (ALA) and linoleic acid (LA). Too much LA overwhelms these enzymes, which only seem to be loosely regulated, and results in an excess of inflammatory AA products and an inadequacy of very long chain omega 3s.

So this adaptation is good for vegetarians eating traditional diets, as in Pune where the traditional fat source would have been ghee, with a little mustard seed oil added. Low in omega 6, balanced in omega 3, enough hearty saturated dairy fat to protect against the diabetogenic effect of a diet high in both starch and sugar.

But think about it - this adaptation isn't some random lucky fluke. For one gene to dominate over another like this, there needs to be some significant and sustained reproductive advantage.
Reproductive advantage means one or more of these - greater fertility, fewer stillbirths, fewer complications of pregnancy, lower mortality early in life, greater attractiveness to a mate.

The vegetarian PUFA polymorphism flourished because, in the past, people without it, eating vegetarian diets, suffered some combination of infertility, stillbirth, dangerous pregnancy, early mortality, or plain butt-ugliness.

Its incidence at present is 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. That to me indicates a burden of suffering and infertility in South Asians in the past, to produce this result - that's how evolution works, that's how Nature selects. If you're European, the chances are that you do need AA and DHA in your food, unless you want to take your chances with lots of vegetable oil - which seems to me a very second-rate, artificial, and dicey way of getting there.

Note that some vegans do think it's okay to eat bivalve shellfish, which can't feel pain (or rather, probably don't feel more pain that plants do, but who knows what that is). This would supply more than enough DHA and AA. However, PETA takes the hard line on this, like the Buddhist who won't swat a zika-carrying mosquito.
But then, PETA is Neal Barnard's baby and he's a dietary cholesterol zealot, so their ban on shellfish might not be as strictly ethical as they claim. Dr Barnard "advises people to avoid added vegetable oils and other high-fat foods as well as refined sugar and flour". Well good for him but it is hard to see where the AA and DHA will come from for the majority of Europeans on this diet.

Maybe veganism is a bit like statinism - enough of the people it's going to harm will drop out of the trial early for the long-term results to look a bit encouraging. It would be interesting to see if long-term vegans in European populations have in fact self-selected for the FADS2 polymorphism common in Pune.